Temporal acuity in developmental dyslexia across the life span : Tactile, auditory, visual, and crossmodal estimations

Taustaa Kehityksellinen dysleksia (lukivaikeus) on erityinen lukemaan oppimisen vaikeus, johon liittyy usein myös vaikeuksia kirjoittamaan oppimisessa. Lukivaikeuden oletetaan useissa tapauksissa johtuvan vaikeudesta käsitellä kielen äännerakenteita (fonologinen prosessointi). Tämä poikkeavuus voi olla joko lukivaikeuden perimmäinen syy tai vaihtoehtoisesti ongelmat äänteiden käsittelyssä voivat heijastaa jotain vielä perustavamman tason vaikeutta. Eräs tällainen ehdotettu perustavan tasoin syy on poikkeavuus aistien toiminnoissa, erityisesti aistien aikatarkkuudessa. Aikatarkkuudella tarkoitetaan kykyä ja rajoja siinä, kuinka nopeasti esitettyä aistitiedon virtaa henkilö kykenee vastaanottamaan ja käsittelemään. Monet arjen toiminnot lukemisen rinnalla edellyttävät aistien erittäin tarkkaa ajallista erottelukykyä (esimerkiksi kuulo puheen ymmärtämisessä, tunto pintamateriaalin tunnistamisessa). Aikatarkkuusvaikeuksien esiintyvyyttä lukivaikeudessa on tutkittu aiemminkin, mutta yksimielisyyteen ei ole päästy siitä, onko kaikilla lukivaikeuksisilla näitä ongelmia tai mihin aisteihin vaikeudet mahdollisesti rajoittuvat. Myöskään ei tiedetä, havaitaanko aikatarkkuuden ongelmia kaiken ikäisillä lukivaikeuksisilla vai vaihteleeko mahdollinen ongelmien kuva iän mukana. Lisäksi on epäselvää, kuinka aikatarkkuuden ongelmat itseasiassa ovat yhteydessä kielen käsittelyn ja varsinaisen lukemisen vaikeuksiin. Tutkimussarjan aihe Tässä tutkimussarjassa aikatarkkuutta tutkittiin kolmessa yksittäisessä aistissa, joita olivat tunto, näkö ja kuulo, sekä kolmessa aistien välisessä yhdistelmässä, joita olivat audiotaktiilinen (kuulo-tunto), visuotaktiilinen (näkö-tunto) ja audiovisuaalinen (näkö-kuulo). Aikatarkkuutta arvioitiin kahdella eri menetelmällä, jotta saataisiin lisää tietoa siitä, missä tietyssä aikatarkkuuden osa-alueessa lukivaikeuksisilla mahdollisesti on vaikeuksia. Ensimmäisessä tehtävässä tutkittavan tuli arvioida, ovatko esitetyt ei-kielelliset ärsykkeet samanaikaisia vai eriaikaisia. Toisessa tehtävässä koehenkilön tuli arvioida esitettyjen ei-kielellisten ärsykkeiden esitysjärjestys. Molemmissa tehtävissä määriteltiin millisekuntitasolla (sekunnin tuhannesosa) se esitysnopeus, jolla koehenkilö kykeni arvioimaan ärsykkeiden ajalliset suhteet oikein. Englanninkielinen demonstraatio aikatarkkuustehtävistä löytyy internetistä (http://www.helsinki.fi/hum/ylpsy/neuropsy). Itse aikatarkkuustehtävien lisäksi tutkimussarjassa arvioitiin tutkimushenkilöiden päättelykykyä, kielellisiä toimintoja ja lukemista. Tutkimushenkilöt Tutkimuksiin osallistui 53 lukivaikeuksista ja 66 sujuvaa lukijaa, jotka oli jaettu kolmeen pääikäryhmään: lapset (8-12 vuotta), nuoret aikuiset (20-36 vuotta) ja ikääntyneemmät aikuiset (20-59 vuotta). Ikääntyneempien aikuisten ryhmä oli edelleen jaettu ikävuosikymmenluokkiin, mikä mahdollisti sen tutkimisen, vaikuttaako lisääntyvä aikuisikä lukivaikeuksisten aikatarkkuuteen (20-29, 30-39, 40-49 ja 50-59 -vuotiaat). Tutkimussarjan tulokset Aikatarkkuuden ongelmat lukivaikeuksisilla olivat yleistyneitä yli iän, aistien ja tehtävien Lukivaikeuksiset kaikissa pääikäryhmissä (lapset, nuoret aikuiset, ikääntyneemmän aikuiset) tarvitsivat samanikäisiä sujuvia lukijoita hitaamman esitystahdin, jotta he kykenivät arvioimaan ei-kielellisten ärsykkeiden ajallisen esitystavan oikein. Tämä aikatarkkuuden ongelma havaittiin lukivaikeuksisilla kaikissa aisteissa (tunto, kuulo, näkö) ja niiden yhdistelmissä (audiotaktiilinen, visuotaktiilinen, audiovisuaalinen). Lukivaikeuksisten aikatarkkuusongelmat ilmenivät edelleen molemmissa tehtävätyypeissä (samanaikaisuuden ja järjestyksen arvioinnissa). Aikatarkkuus ja sen ongelmat olivat yhteydessä äänteiden käsittelyyn Aikatarkkuus oli yhteydessä äänteiden käsittelykykyyn (fonologiseen prosessointiin), niin lapsilla kuin aikuisillakin, kaikissa aisteissa, niiden yhdistelmissä ja tehtävätyypeissä. Yhteys ei-kielellisen aikatarkkuuden ja kielellisten toimintojen välillä oli kuitenkin selkeämpi lukivaikeuksisilla kuin sujuvilla lukijoilla. Tämä tarkoittaa, että etenkin lukivaikeuksisilla ryhmätason huono aikatarkkuus oli yhteydessä huonoon äänteiden käsittelyyn (fonologiseen prosessointiin) ja päinvastoin. Suoraa yhteyttä lukemisen ja aikatarkkuuden välillä ei kuitenkaan havaittu. Lisääntyvä aikuisikä heikensi lukivaikeuksisten aikatarkkuutta suhteettoman paljon Tiedonkäsittelyn nopeuden on toistuvasti osoitettu hidastuvan normaalissa ikääntymisessä. Lisääntyvä aikuisikä (20-59 -vuotiailla) heikensikin sekä sujuvien että lukivaikeuksisten aikatarkkuutta. Toisin sanoen, mitä iäkkäämmästä aikuisesta oli kysymys, sitä hitaammin hänelle tuli esittää ärsykkeet, jotta hän kykeni arvioimaan niiden ajalliset suhteet oikein. Tämä ikään liittyvä tavanomainen hidastuminen oli kuitenkin yllättäen suhteettoman nopeaa lukivaikeuksisilla. Toisin sanoen, jo nuorilla lukivaikeuksisilla havaittu aikatarkkuuden vaikeus (ryhmäero verrattuna sujuviin lukijoihin) ei pysynyt saman suuruisena, vaan ryhmien ero kasvoi aikuisiän lisääntyessä. Tulosten merkitys Lukivaikeuden osoitettiin tässä tutkimussarjassa olevan yhteydessä yleistyneeseen vaikeuteen käsitellä ajassa nopeasti muuttuvaa ei-kielellistä aistitietoa (yli aistien ja niiden yhdistelmien, tehtävätyyppien, tutkittavien iän). Tämä osoittaa, että lukivaikeus ei ole ongelma, joka rajoittuu vain kielellisen materiaalin käsittelyn vaikeuksiin (äänteiden käsittely, lukeminen, kirjoittaminen). Nyt havaitut vaikeudet eivät myöskään rajoittuneet vain niihin aisteihin, jotka selkeimmin liittyvät lukemiseen (näkö) ja puhuttuun kieleen (kuulo); Ongelmia esiintyi myös muissa aisteissa (tunto). Lukivaikeuksisten lukijoiden ryhmätasolla havaittu aikatarkkuuden ongelma ei kuitenkaan heijastunut yksilötasolle; Jokainen lukivaikeuksinen ei ollut huono aikatarkkuustehtävissä. Näin ollen ei siis voida väittää, että kaikkien lukivaikeuksisten äänteiden käsittelyn tai lukemaan oppimisen vaikeudet voisivat selittyä aistien toimintojen poikkeavuudella. Aikatarkkuuden ongelmat eivät olleet yhteydessä varsinaiseen lukemiseen. Sekä lukivaikeuksisilla lapsilla että aikuisilla todettiin kuitenkin selkeä yhteys aikatarkkuuden ongelmien ja lukemaan oppimisen keskeisen ennakkoehdon, fonologisen prosessoinnin, välillä. Saattaa siis olla, että synnynnäinen aistien toimintojen poikkeavuus vaikuttaa yksilön suoriutumiseen jo ennen varsinaista lukemaan oppimista, kun ne taidot kehittyvät (fonologinen prosessointi), joille myöhempi lukemaan oppiminen perustuu. Ikäännyttäessä havaittu lukivaikeuksisten suhteettoman nopea aikatarkkuuden heikkeneminen osoittaa, että lukivaikeus ei voi olla ongelma, joka koskee vain lapsuusikää, tai vaikeus, joka johtuu vain kehityksen viivästymästä joka kurottaisiin iän myötä umpeen. Tulosten ymmärtämiseksi onkin muistettava kaksi seikkaa. Lukivaikeus on ensinnäkin yhdistetty synnynnäisiin, pieniin, poikkeavuuksiin aivojen rakenteissa ja toiminnoissa. Toisaalta tavanomaiseen ikääntymiseen liittyy se, että aivot kykenevät yhä huonommin korjaamaan ja kiertämään (kompensoimaan) pieniä vaurioita. Tämän perusteella tutkimussarjan tuloksista voidaan päätellä, että lukivaikeuksisten jo synnynnäisesti heikentyneet aivojen kompensointimahdollisuudet eivät ole yhtä tehokkaita puskuroimaan ikääntymisen tavanomaisia vaikutuksia kuin sujuvilla lukijoilla. Yllättävää kuitenkin on, että tämä korostunut heikkeneminen havaittiin jo suhteellisen nuorilla, työikäisillä, lukivaikeuksisilla, ennen 60 ikävuotta. Samanlaista ikäännyttäessä korostuvaa vaikeutta ei lukivaikeuksilla kuitenkaan havaittu päättelyssä, kielellisissä toiminnoissa tai itse lukemisessa. Vaikuttaakin siis siltä, että ne toiminnot, joita on harjaannutettu aktiivisesti, eivät heikkene kasvavan aikuisiän myötä yhtä suhteettomasti. Alkuperäiset artikkelit Laasonen M, Tomma-Halme J, Lahti-Nuuttila P, Service E, and Virsu V (2000) Rate of information segregation in developmentally dyslexic children, Brain and Language, 75(1), 66-81. Laasonen M, Service E, and Virsu V (2001) Temporal order and processing acuity of visual, auditory, and tactile perception in developmentally dyslexic young adults, Cognitive, Affective, and Behavioral Neuroscience, 1(4), 394-410. Laasonen M, Service E, and Virsu V (2002) Crossmodal temporal order and processing acuity in developmentally dyslexic young adults, Brain and Language, 80(3), 340-354. Laasonen M, Lahti-Nuuttila P, and Virsu V (2002) Developmentally impaired processing speed decreases more than normally with age, NeuroReport, 13(9), 1111-1113.

Identtisten ja epäidenttisten kaksosten puhe : Monotsygoottisten ja ditsygoottisten kaksosten puheen vertailua kesto-, nopeus-, tauko- ja taajuusmittauksin

This thesis presents an experimental study of the speech prosody of identical and non-identical twins. Speech fluency, pauses, speech rate, utterance length and speech frequency were examined phonetically, auditorily, semantically and statistically. The methods included both reading tasks (reading the alphabet, numerical lists, sentences with foreign loan words, holiday theme questions as well as 1.5 pages of text with long sentences and complex words) and spontaneous speech tasks (picture description and answering holiday theme questions). The subjects were Finnish-speaking 22-28-year-old female twins: 8 identical (monozygotic) and 10 non-identical (dizygotic) pairs. One pair was male-female. Comparisons were made between twin groups and between sisters. The data was regathered from four twin pairs, to make it possible to investigate some subjects intra-individually. In addition phoneticians, phonetic students and people without knowledge of phonetic science were tested in two listening experiments. The results showed that the dizygotic twins differed more from each other than monozygotic twins and that monozygotic twin sisters shared more similarities than dizygotic twin sisters. For example, between monozygotic twin sisters smaller differences were found between word count, utterance length and speech rate in spontaneous speech tasks. Dizygotic twin sisters made more different kinds of reading mistakes with the same target words than monozygotic twin sisters, while monozygotic twin sisters made more of the same reading mistakes with the same target words than dizygotic twin sisters. The listening experiments showed that only professional phoneticians were able to recognize the twin sisters. Even though the twins had the possibility to freely choose their speech rate, pausing and speech frequency, they used their own speech patterns; these included the same average speech frequency, average speech rate, type of pausing routine or filled pauses, and other speech mannerisms throughout their speech.

Finnish Homicides and Mental Disorders: An investigation of offense and offender characteristics

Although the majority of people with mental illness are not violent, scientific studies over the last decades show that certain psychiatric disorders increase the risk of violent behavior, including homicide. This thesis examined crime scene behaviors and offender background characteristics among mentally ill Finnish homicide offenders. Previously, homicide crime scene behaviors have been investigated in relation to offender demographic characteristics, whereas this study compares the behaviors of offenders with various mental illnesses. The study design was a retrospective chart review of the forensic psychiatric statements of Finnish homicide offenders. The work consists of four substudies. The aims of the study were as follows: To describe differences in the childhood and family backgrounds as well as in the adolescent and adult adjustment of Finnish homicide offenders belonging to different diagnostic categories (schizophrenia, personality disorder, alcoholism, drug addiction or no diagnosis). Further, the study examined associations between the crime scene behaviors and mental status of these offenders. Also, the distinguishing characteristics between two groups of offenders with schizophrenia were examined: early starters, who present antisocial behavior before the onset of schizophrenia, and late starters, who first offend after the onset of mental disorder. Finally, it was investigated how the use of excessive violence is associated with clinical and circumstantial variables as well as offender background characteristics among homicide offenders with schizophrenia. The main findings of the study can be summarized as follows. First, offenders with personality disorder or drug addiction had experienced multiple difficulties in their early environments: both family and individual problems were typical. Offenders with schizophrenia were relatively well-adjusted in childhood compared to the other groups. However, in adolescence and adulthood, social isolation, withdrawal and other difficulties attributable to these offenders illness became evident. In several aspects, offenders with alcohol dependency resembled offenders with no diagnosis in that these offenders had less problematic backgrounds compared to other groups. Second, the results showed that crime scene behaviors, victim gender and the victim-offender relationship differ between the groups. In particular, offenders with a diagnosis of schizophrenia or drug addiction have some unique features in their crime scene behaviors and choice of victims. Offenders with schizophrenia were more likely to kill a blood relative, to use a sharp weapon and to injure the victim s face. Drug addiction was associated with stealing from the victim and trying to cover up the body. Third, the results suggest that the offense characteristics of early- and late-start offenders with schizophrenia differ only modestly. However, several significant differences between the groups were found in characteristics of offenders: early starters had experienced a multitude of problems in their childhood surroundings and also later in life. Fourth, violent acts where the offender did not commit the offense alone or had previous homicidal history were predictive of excessive violence among offenders with schizophrenia. Positive psychotic symptoms did not predict the use of excessive violence. Nearly one third of the cases in the sample involved multiple and severe violence, including features such as sadism, mutilation, sexual components or extreme stabbing. In sum, mentally disordered homicide offenders are heterogeneous in their offense characteristics as well as their background characteristics. Empirically based information on how the offender s mental state is associated with specific crime scene behaviors can be utilized within the police force in developing methods of prioritizing suspects in unsolved homicide cases. Also, these results emphasise the importance of early interventions for problem families and children at risk of antisocial behavior. They may also contribute to the development of effective treatment for violent offenders.

Lionhearts of the Playworld : An ethnographic case study of the development of agency in play pedagogy

This is an ethnographic case study of the creation and emergence of a playworld – a pedagogical approach aimed at promoting children’s development and learning in early education settings through the use of play and drama. The data was collected in a Finnish experimental mixed-age elementary school classroom in the school year 2003-2004. In the playworld students and teachers explore different social and cultural phenomena through taking on the roles of characters from a story or a piece of literature and acting inside the frames of an improvised plot. The thesis takes under scrutiny the notion of agency in education. It produces theoretically grounded empirical knowledge of the ways in which children struggle to become recognized and agentive actors in early education settings and how their agency develops in their interaction with adults. The study builds on the activity theoretical and sociocultural tradition and develops a methodological framework called video-based narrative interaction analysis for studying student agency as developing over time but manifesting through the situational material and discursive local interactions. The research questions are: 1. What are the children’s ways of enacting their agency in the playworld? 2. How do the children’s agentive actions change and develop over the spring? 3. What are the potentials and challenges of the playworld for promoting student agency? 4. How do the teachers and the children deal with the contradiction between control and agency in the playworld? The study consists of a summary part and four empirical articles which each have a particular viewpoint. Articles I and II deal with individual students’ paths to agency. In Article I the focus is on the role of resistance and questioning in enabling important spaces for agency. Article II takes a critical gender perspective and analyzes how two girls struggled towards recognition in the playworld. It also illuminates the role of imagination in developing a sense of agency. Article III examines how the open-ended and improvisational nature of the playworld interaction provided experiences and a sense of ‘shared agency’ for the students and teachers in the class. Article IV turns the focus on the teachers and analyzes how their role actions in the playworld helped the children to enact agency. It also discusses the challenges that the teachers faced in this work and asks what makes the playworld activity sustainable in the class. The summary part provides a critical literature review on the concept of agency and argues that the inherently contradictory nature of the phenomenon of agency has not been sufficiently theorized. The summary part also locates the playworld intervention in a historical frame by discussing the changing conceptions of adulthood and childhood in the West. By focusing on the changing role of play and art in both adults’ and children’s contemporary lives, the thesis opens up an important but often neglected perspective on the problem of promoting student agency in education. The results illustrate how engaging in a collectively imagined and dramatized pretend play space together with the children enabled the teachers to momentarily put aside their “knower” positions in the classroom. The fictive roles and the narrative plot helped them to create a necessary incompleteness and open-endedness in the activity that stimulated the children’s initiatives. This meant that the children too could momentarily step out of their traditional classroom positions as pupils and initiate action to further the collective play. Engaging in this kind of unconventional activity and taking up and enacting agency was, however, very challenging for the participating children and teachers. It often contradicted the need to sustain control and order in the classroom. The study concludes that play- and drama-based pedagogies offer a unique but undeveloped potential for developing educational spaces that help teachers and children deal with the often contradictory requirements of schooling.

Vammaisen lapsen äidin vanhemmuuden kokemus sekä lähiympäristön ja kasvatuskumppanuuden merkitys

The parenthood experience of a mother with a disabled child and the meaning of the social environment and parent-professional partnerships The importance of parental guidance when a family has a child with a disability or autism has been pointed out by several studies. The present research was based on the premise that by supporting the mother we can help the whole family to cope better and the professionals in day care or at school are able to support parents. The starting point was the subjective experience, which is also the central focus of the phenomenological method. The purpose of this study was firstly to describe the experience of the mother and the dialogue between mother and educational professionals. Secondly it was the task of this research to discover what kind of support and information the mother obtains from her social environment. At the background of this study there was the ecological theory of Bronfenbrenner, the ecocultural approach by Gallimore and the interactive examination of family that take into consideration the whole environment and personal situation. The research data was collected by interviewing the mothers, the day care personnel and the teachers at school. In this research there were a total of 32 interviews and 24 informants: 10 mothers who have a child with a disability and/or autism, 8 professionals in day care and 6 teachers at school. This study was longitudinal because the same mothers were interviewed twice, first in 1998 and then after five years in 2003. It was thus possible to get information on whether their life situation had changed and the nature of those changes. The data of this study was analysed by the method of phenomenological psychology that was applied for this study. The findings indicated that all mothers had experienced many complicated emotional feelings such as: anger, mourning, fear and sadness as well as love and bonding. It can be said that several human feelings existed at the same time. Mothers experienced that the support of the social environment, for example, relatives, families in the same situation and persons taking care of the child had significant meaning for their coping. However the life situation among the mothers varied. Mostly mothers received valuable support for their parenthood and they have adopted a strong emotion for manage ring. Mothers with an autistic child were more stressed than mothers with a mentally retarded child. A few mothers had numerous problems with taking care of their child and they did not get enough help. Same mothers were very exhausted too and the situation was quite the same after five years, when their child was teenager. All mothers said that after starting school the support for the family had significally diminished. Mothers said that dialogue with teacher got on without problems, but there were meetings seldom, so it wasn´t possible to get enough support for their parenthood. Keywords: parenthood, motherhood, disability, early special education, family-centred.

Semanttisen webin ontologisen tekstiilikäsitteistön kehittäminen ja liittäminen museoiden luettelointitietoihin

DEVELOPING A TEXTILE ONTOLOGY FOR THE SEMANTIC WEB AND CONNECTING IT TO MUSEUM CATALOGING DATA The goal of the Semantic Web is to share concept-based information in a versatile way on the Internet. This is achievable using formal data structures called ontologies. The goal of this re-search is to increase the usability of museum cataloging data in information retrieval. The work is interdisciplinary, involving craft science, terminology science, computer science, and museology. In the first part of the dissertation an ontology of concepts of textiles, garments, and accessories is developed for museum cataloging work. The ontology work was done with the help of thesauri, vocabularies, research reports, and standards. The basis of the ontology development was the Museoalan asiasanasto MASA, a thesaurus for museum cataloging work which has been enriched by other vocabularies. Concepts and terms concerning the research object, as well as the material names of textiles, costumes, and accessories, were focused on. The research method was terminological concept analysis complemented by an ontological view of the Semantic Web. The concept structure was based on the hierarchical generic relation. Attention was also paid to other relations between terms and concepts, and between concepts themselves. Altogether 977 concept classes were created. Issues including how to choose and name concepts for the ontology hierarchy and how deep and broad the hierarchy could be are discussed from the viewpoint of the ontology developer and museum cataloger. The second part of the dissertation analyzes why some of the cataloged terms did not match with the developed textile ontology. This problem is significant because it prevents automatic ontological content integration of the cataloged data on the Semantic Web. The research datasets, i.e. the cataloged museum data on textile collections, came from three museums: Espoo City Museum, Lahti City Museum and The National Museum of Finland. The data included 1803 textile, costume, and accessory objects. Unmatched object and textile material names were analyzed. In the case of the object names six categories (475 cases), and of the material names eight categories (423 cases), were found where automatic annotation was not possible. The most common explanation was that the cataloged field was filled with a long sentence comprised of many terms. Sometimes in the compound term, the object name and material, or the name and the way of usage, were combined. As well, numeric values in the material name cataloging field prevented annotation and so did the absence of a corresponding concept in the ontology. Ready-made drop-down lists of materials used in one cataloging system facilitated the annotation. In the case of naming objects and materials, one should use terms in basic form without attributes. The developed textile ontology has been applied in two cultural portals, MuseumFinland and Culturesampo, where one can search for and browse information based on cataloged data using integrated ontologies in an interoperable way. The textile ontology is also part of the national FinnONTO ontology infrastructure. Keywords: annotation, concept, concept analysis, cataloging, museum collection, ontology, Semantic Web, textile collection, textile material

Erityistä tukea tarvitsevien lasten polut esiopetuksesta alkuopetukseen : tukitoimet ja suoriutuminen

The purpose of this follow-up study is to analyse stages of learning and teaching of children with special needs in pre-school and the first two grades of elementary school. The target group included 270 children with special needs. The three year follow-up period for each child began during the pre-school year, and continued until the spring of the second grade in elementary school. Various diagnoses were detected among children in the study group. The disorders were categorised in six classes: the developmentally delayed, children with language development disorder, children with emotional and behavioural disorders, children with attention deficit, children with other non-cognitive disorders and children with extensive developmental disorders. The study's starting point was the situation in pre-school: how the children were placed in pre-school, and what kinds of support they were offered? The purpose of the study was to describe how children with special needs move from different types of groups in pre-school to the different types of classes in the first two grades of elementary school. I also examined how well the children with special needs succeeded in the first two grades of elementary school. An additional purpose was to find out what connections there may be between the paths taken by children with special needs when they move from pre-school to elementary school, the types of support they get, and how they succeed academically in elementary school. The data were gathered mainly by means of questionnaires. In addition the children were studied by means of tests designed to estimate their academic skills at the end of the second grade. In analysing the data I used both quantitative and qualitative methods. Six paths were identified among the children in the study group, based on whether a child was in a group or a class given special teaching or in an ordinary group or class during pre-school and the first two grades of elementary school. In this study, about 53% of the children with special needs moved from pre-school to a regular class in elementary school, and about 47% of the children received special education in elementary school. Among the ordinary groups (n = 69) in pre-school the majority of children (73 %) moved to a regular class in elementary school. Among the children receiving special education (n = 201) in pre-school, 46% moved to a regular class in elementary school. That path turned out to be the one followed by the greatest number of children. Only rarely did children move from an ordinary group in pre-school to a special education class in elementary school. Examination of the results according to the children's transition paths also links together with the viewpoint of integration and segregation. This study indicates that in pre-school special education groups, a significantly greater number of methods supporting children's development were used than in the conventional education groups. The difference was at its greatest inconnection with the use of so-called special rehabilitation methods. A quite wide range of variation was observed in how the children succeeded in elementary school. Success in the tests designed to estimate the children's academic skills was poor for 31% of the children (n = 230) in the first grade study group. For 69 % of the children, however, success in the tests was at least satisfactory. In the second grade study group 34 % of the children (N = 216) got through all the three tests estimating academic skills acceptably. According to this study, a number of children with special needs require special support throughout pre-school and the first two grades of elementary school. The results show that if the children received special support during the pre-school year, a number were able to participate in regular education in elementary school. Keywords: a child with special needs, measures of support, transitions, achievements in school

Visuaalis-spatiaalisten työmuistivalmiuksien yhteys (esi)matemaattisiin taitoihin ja merkitys osana matemaattisilta taidoiltaan heikkojen lasten ja nuorten kognitiivista profiilia

Tämän itsenäisistä osatutkimuksista koostuvan tutkimussarjan tavoitteena oli pyrkiä täydentämään kuvaa matemaattisilta taidoiltaan heikkojen lasten ja nuorten tiedonkäsittelyvalmiuksista selvittämällä, ovatko visuaalis-spatiaaliset työmuistivalmiudet yhteydessä matemaattiseen suoriutumiseen. Teoreettinen viitekehys rakentui Baddeleyn (1986, 1997) kolmikomponenttimallin ympärille. Työmuistikäsitys oli kuitenkin esikuvaansa laajempi sisällyttäen visuaalis-spatiaaliseen työmuistiin Cornoldin ja Vecchin (2003) termein sekä passiiviset varastotoiminnot että aktiiviset prosessointitoiminnot. Yhteyksiä työmuistin ja matemaattisten taitojen välillä tarkasteltiin viiden eri osatutkimuksen avulla. Kaksi ensimmäistä keskittyivät alle kouluikäisten lukukäsitteen hallinnan ja visuaalis-spatiaalisten työmuistivalmiuksen tutkimiseen ja kolme jälkimmäistä peruskoulun yhdeksäsluokkalaisten matemaattisten taitojen ja visuaalis-spatiaalisten työmuistitaitojen välisten yhteyksien selvittämiseen. Tutkimussarjan avulla pyrittiin selvittämään, ovatko visuaalis-spatiaaliset työmuistivalmiudet yhteydessä matemaattiseen suoriutumiseen sekä esi- että yläkouluiässä (osatutkimukset I, II, III, IV, V), onko yhteys spesifi rajoittuen tiettyjen visuaalis-spatiaalisten valmiuksien ja matemaattisen suoriutumisen välille vai onko se yleinen koskien matemaattisia taitoja ja koko visuaalis-spatiaalista työmuistia (osatutkimukset I, II, III, IV, V) tai työmuistia laajemmin (osatutkimukset II, III) sekä onko yhteys työmuistispesifi vai selitettävissä älykkyyden kaltaisella yleisellä päättelykapasiteetilla (osatutkimukset I, II, IV). Tutkimussarjan tulokset osoittavat, että kyky säilyttää ja käsitellä hetkellisesti visuaalis-spatiaalista informaatiota on yhteydessä matemaattiseen suoriutumiseen eikä yhteyttä voida selittää yksinomaan joustavalla älykkyydellä. Suoriutuminen visuaalis-spatiaalista työmuistia mittaavissa tehtävissä on yhteydessä sekä alle kouluikäisten esimatemaattisten taitojen hallintaan että peruskoulun yhdeksäsluokkalaisten matematiikan taitoihin. Matemaattisilta taidoiltaan heikkojen lasten ja nuorten visuaalis-spatiaalisten työmuistiresurssien heikkoudet vaikuttavat kuitenkin olevan sangen spesifejä rajoittuen tietyntyyppisissä muistitehtävissä vaadittaviin valmiuksiin; kaikissa visuaalis-spatiaalisen työmuistin valmiuksia mittaavissa tehtävissä suoriutuminen ei ole yhteydessä matemaattisiin taitoihin. Työmuistivalmiuksissa ilmenevät erot sekä alle kouluikäisten että kouluikäisten matemaattisilta taidoiltaan heikkojen ja normaalisuoriutujien välillä näyttävät olevan kuitenkin jossain määrin yhteydessä kielellisiin taitoihin viitaten vaikeuksien tietynlaiseen kasautumiseen; niillä matemaattisesti heikoilla, joilla on myös kielellisiä vaikeuksia, on keskimäärin laajemmat työmuistiheikkoudet. Osalla matematiikassa heikosti suoriutuvista on näin ollen selvästi keskimääräistä heikommat visuaalis-spatiaaliset työmuistivalmiudet, ja tämä heikkous saattaa olla yksi mahdollinen syy tai vaikeuksia lisäävä tekijä heikon matemaattisen suoriutumisen taustalla. Visuaalis-spatiaalisen työmuistin heikkous merkitsee konkreettisesti vähemmän mentaalista prosessointitilaa, joka rajoittaa oppimista ja suoritustilanteita. Tiedonkäsittelyvalmiuksien heikkous liittyy nimenomaan oppimisnopeuteen, ei asioiden opittavuuteen sinänsä. Mikäli oppimisympäristö ottaa huomioon valmiuksien rajallisuuden, työmuistiheikkoudet eivät todennäköisesti estä asioiden oppimista sinänsä. Avainsanat: Työmuisti, visuaalis-spatiaalinen työmuisti, matemaattiset taidot, lukukäsite, matematiikan oppimisvaikeudet

Anthraquinones from the Fungus Dermocybe sanguinea as Textile Dyes

This study is based on the multidiciplinary approach of using natural colorants as textile dyes. The author was interested in both the historical and traditional aspects of natural dyeing as well as the modern industrial applications of the pure natural compounds. In the study, the anthraquinone compounds were isolated as aglycones from the ectomycorrhizal fungus Dermocybe sanguinea. The endogenous beta-glucosidase of the fungus was used to catalyse the hydrolysis of the O-glycosyl linkage in emodin- and dermocybin-1-beta-D-glucopyranosides. The method, in which 10.45 kg of fresh fungi was starting material, yielded two fractions: 56.0 g of Fraction 1 (94% of the total amount of pigment,) consisting almost exclusively of the main pigments emodin and dermocybin, and 3.3 g of Fraction 2 (6%) consisting mainly of the anthraquinone carboxylic acids. The anthraquinone compounds in Fractions 1 and 2 were separated by one- and two-dimensional thin-layer-chromatography (TLC) using silica plates. 1D TLC showed that neither an acidic nor a basic solvent system alone separated completely all the anthraquinones isolated from D. sanguinea, in spite of the variation of the rations of the solvent components in the systems. Thus, a new 2D TLC technique was developed, applying n-pentanol-pyridine-methanol (6:4:3, v/v/v) and toluene-ethyl acetate-ethanol-formic acid (10:8:1:2, v/v/v/v) as eluents. Fifteen different anthraquinone derivatives were completely separated from one another. Emodin, physcion, endocrocin, dermolutein, dermorubin, 5-chlorodermorubin, emodin-1-beta-D-glucopyranoside, dermocybin-1-beta-D-glucopyranoside and dermocybin, and five new compounds, not earlier identified in D. sanguinea, 7-chloroemodin, 5,7-dichloroemodin, 5,7-dichloroendocrocin, 4-hydroxyaustrocorticone and austrocorticone, were separated and identified on the basis of their Rf-values, UV/Vis spectra and mass spectra. One substance remained unidentified, because of its very low concentration. The anthraquinones in Fractions 1 and 2 were preparatively separeted by liquid-liquid partition, with isopropylmethyl ketone and aqueous phosphate buffer as the solvent system. Advantage was taken of the principle of stepwise pH-gradient elution. The multiple liquid-liquid partition (MLLP) offered an excellent method for the preparative separation of compounds, which contain acidic groups such as the phenolic OH and COOH groups. Due to their strong aggregation properties, these compounds are, without derivatization, very difficult to separate on a preparative scale by chromatographic methods. By the MLLP method remarkable separations were achieved for the components in each mixture. Emodin and dermocybin were both obtained from Fraction 1 in a purity of at least 99%. Pure emodin and dermocybin were applied as mordant dyes to wool and polyamide and as disperse dyes to polyester and polyamide, using the high temperature (HT) technique. A mixture of dermorubin and 5-chlorodermorubin was applied as an acid dye to wool. In these experiments, synthetic dyes were used as references. Experiments were also performed using water extract of the air-dried fungi as dye liquor for wool and silk. The main colouring compounds in the crude water extract were emodin and dermocybin, which indicated that the O-glycosyl linkages in emodin- and dermocybin-1-beta-D-glucopyranosides were broken by the beta-glucosidase enzyme. Apparently, the hydrolysis occurred during the drying of the fungi and during the soaking of the dried fruit bodies overnight when preparing the dyebath. The colour of each dyed material was investigated in terms of the CIELAB L*, a* and b* values, and the colour fastness to light, washing and rubbing was tested according to the ISO standards. In the mordant dyeing experiments, emodin dyed wool and polyamide yellow and red, depending on the pH of the dyebath. Dermocybin gave purple and violet colours. The colour fastness of the mordant-dyed fabrics varied from good to moderate. The fastness properties of the natural anthraquinone carboxylic acids on wool were good, indicating the strength of the ionic bonds between the COO- groups of the dyes and the NH3+ groups of the fibres. In the disperse dyeing experiments, emodin dyed polyester bright yellow and dermocybin bright reddish-orange, and the fabrics showed excellent colour fastness. In contrast, emodin and dermocybin successfully dyed polyamide brownish-orange and wine-red, respectively, but with only moderate fastness. In industrial dyeing processes, natural anthraquinone aglycone mixtures dyed wool and silk well even at low concentrations of mordants, i.e. with 10% of the weight of the fibre (owf) of KAl(SO4)2 and 1 or 0.5% owf of other mordants. This study showed that purified natural anthraquinone compounds can produce bright hues with good colour-fastness properties in different textile materials. Natural anthraquinones have a significant potential for new dyeing techniques and will provide useful alternatives to synthetic dyes.

Aritmetiikasta algebraan : Muutoksia osaamisessa peruskoulun päättöluokalla 20 vuoden aikana

From Arithmetic to Algebra. Changes in the skills in comprehensive school over 20 years. In recent decades we have emphasized the understanding of calculation in mathematics teaching. Many studies have found that better understanding helps to apply skills in new conditions and that the ability to think on an abstract level increases the transfer to new contexts. In my research I take into consideration competence as a matrix where content is in a horizontal line and levels of thinking are in a vertical line. The know-how is intellectual and strategic flexibility and understanding. The resources and limitations of memory have their effects on learning in different ways in different phases. Therefore both flexible conceptual thinking and automatization must be considered in learning. The research questions that I examine are what kind of changes have occurred in mathematical skills in comprehensive school over the last 20 years and what kind of conceptual thinking is demonstrated by students in this decade. The study consists of two parts. The first part is a statistical analysis of the mathematical skills and their changes over the last 20 years in comprehensive school. In the test the pupils did not use calculators. The second part is a qualitative analysis of the conceptual thinking of pupils in comprehensive school in this decade. The study shows significant differences in algebra and in some parts of arithmetic. The largest differences were detected in the calculation skills of fractions. In the 1980s two out of three pupils were able to complete tasks with fractions, but in the 2000s only one out of three pupils were able to do the same tasks. Also remarkable is that out of the students who could complete the tasks with fractions, only one out of three pupils was on the conceptual level in his/her thinking. This means that about 10% of pupils are able to understand the algebraic expression, which has the same isomorphic structure as the arithmetical expression. This finding is important because the ability to think innovatively is created when learning the basic concepts. Keywords: arithmetic, algebra, competence

"Haluan tuonne heti!" : Tulevaisuuskuvia ghanalaisten, isobritannialaisten,suomalaisten ja tansanialaisten lasten piirustuksissa

"I want there now!" Images of the future in the drawings of Ghanaian, British, Finnish and Tanzanian children The aim of the Thesis is to examine what kind of images children aged between 8 and 12 years in Ghana, Great Britain, Finland and Tanzania hold of their future. The study is a qualitative analysis based on data that consists of 214 drawings, digitally photographed and analysed using AtlasTI computer program. The data was coded and divided into " families " whose frequencies were compared in order to maintain results. The assignment was given to the children in the language used in the school and it was similar in each country. The children were introduced to the idea with a set of stimulating questions and after that they were asked to draw and colour with a pen a picture of 1) him/herself as an adult, 2) his/her future home and 3) the people and the animals they think they will be living with. The children were also asked to write down the country and the place they believe to live in their future. They were also encouraged to write down e.g. their dream profession, what they would like to have as hobbies in their adulthood and other important things in their lives. The analysis focuses on the content of the drawings instead of artistic or psychological interpretations. The differences between the drawings from different countries as well as the differences in a single country were significant. The current trends and the experiences children had lived through were present in the drawings. There were no differences in the colour of the skin and the most popular professions were doctor, police and football player. The football was very strongly present in all of the data; almost fourth of the children had either drawn or mentioned football as their future profession or hobby. Different flora was present in 84% of Tanzanian and 70% of Ghanaian drawings compared to the 23% of British and 17% of Finnish drawings. Of all the family forms a dream of the traditional nuclear family could be found among 29% of the drawings. Compared to that a total of 30% wanted either a child of their own without a spouse (15%) or a spouse without a child (15%). Also grandparents, childhood friends, other adults, animals or even space aliens were present and sharing a home with the children in the drawings. Of all children 15% wanted to live totally alone in the future. This was most typical (38%) among the Finnish boys. The cat and the dog were the most popular animals to appear in the drawings. Moving abroad proved to be purely a western phenomenon, dreamed by 57% of the British and 18% of the Finnish children. As results, a negative self-image, violence, lack of expressions of positive feelings and solitude among the Finnish boys in the data were very concerning. Keywords: Images of the future, future studies, future-education, picture analysis

Adenoviral Gene Therapy for Advanced Head and Neck Cancer

Advanced stage head and neck cancers (HNC) with distant metastasis, as well as prostate cancers (PC), are devastating diseases currently lacking efficient treatment options. One promising developmental approach in cancer treatment is the use of oncolytic adenoviruses, especially in combination therapy with conventional cancer therapies. The safety of the approach has been tested in many clinical trials. However, antitumor efficacy needs to be improved in order to establish oncolytic viruses as a viable treatment alternative. To be able to test in vivo the effects on anti-tumor efficiency of a multimodal combination therapy of oncolytic adenoviruses with the standard therapeutic combination of radiotherapy, chemotherapy and Cetuximab monoclonal antibody (mAb), a xenograft HNC tumor model was developed. This model mimics the typical clinical situation as it is initially sensitive to cetuximab, but resistance develops eventually. Surprisingly, but in agreement with recent findings for chemotherapy and radiotherapy, a higher proportion of cells positive for HNC cancer stem cell markers were found in the tumors refractory to cetuximab. In vitro as well as in vivo results found in this study support the multimodal combination therapy of oncolytic adenoviruses with chemotherapy, radiotherapy and monoclonal antibody therapy to achieve increased anti-tumor efficiency and even complete tumor eradication with lower treatment doses required. In this study, it was found that capsid modified oncolytic viruses have increased gene transfer to cancer cells as well as an increased antitumor effect. In order to elucidate the mechanism of how oncolytic viruses promote radiosensitization of tumor cells in vivo, replicative deficient viruses expressing several promising radiosensitizing viral proteins were tested. The results of this study indicated that oncolytic adenoviruses promote radiosensitization by delaying the repair of DNA double strand breaks in tumor cells. Based on the promising data of the first study, two tumor double-targeted oncolytic adenoviruses armed with the fusion suicide gene FCU1 or with a fully human mAb specific for human Cytotoxic T Lymphocyte-Associated Antigen 4 (CTLA-4) were produced. FCU1 encodes a bifunctional fusion protein that efficiently catalyzes the direct conversion of 5-FC, a relatively nontoxic antifungal agent, into the toxic metabolites 5-fluorouracil and 5-fluorouridine monophosphate, bypassing the natural resistance of certain human tumor cells to 5-fluorouracil. Anti-CTLA4 mAb promotes direct killing of tumor cells via apoptosis and most importantly immune system activation against the tumors. These armed oncolytic viruses present increased anti-tumor efficacy both in vitro and in vivo. Furthermore, by taking advantage of the unique tumor targeted gene transfer of oncolytic adenoviruses, functional high tumor titers but low systemic concentrations of the armed proteins were generated. In addition, supernatants of tumor cells infected with Ad5/3-24aCTLA4, which contain anti-CTLA4 mAb, were able to effectively immunomodulate peripheral blood mononuclear cells (PBMC) of cancer patients with advanced tumors. -- In conclusion, the results presented in this thesis suggest that genetically engineered oncolytic adenoviruses have great potential in the treatment of advanced and metastatic HNC and PC.

Developmental, functional brain imaging and electrophysiological evidence of visual and auditory working memory

Intact function of working memory (WM) is essential for children and adults to cope with every day life. Children with deficits in WM mechanisms have learning difficulties that are often accompanied by behavioral problems. The neural processes subserving WM, and brain structures underlying this system, continue to develop during childhood till adolescence and young adulthood. With functional magnetic resonance imaging (fMRI) it is possible to investigate the organization and development of WM. The present thesis aimed to investigate, using behavioral and neuroimaging methods, whether mnemonic processing of spatial and nonspatial visual information is segregated in the developing and mature human brain. A further aim in this research was to investigate the organization and development of audiospatial and visuospatial information processing in WM. The behavioral results showed that spatial and nonspatial visual WM processing is segregated in the adult brain. The fMRI result in children suggested that memory load related processing of spatial and nonspatial visual information engages common cortical networks, whereas selective attention to either type of stimuli recruits partially segregated areas in the frontal, parietal and occipital cortices. Deactivation mechanisms that are important in the performance of WM tasks in adults are already operational in healthy school-aged children. Electrophysiological evidence suggested segregated mnemonic processing of visual and auditory location information. The results of the development of audiospatial and visuospatial WM demonstrate that WM performance improves with age, suggesting functional maturation of underlying cognitive processes and brain areas. The development of the performance of spatial WM tasks follows a different time course in boys and girls indicating a larger degree of immaturity in the male than female WM systems. Furthermore, the differences in mastering auditory and visual WM tasks may indicate that visual WM reaches functional maturity earlier than the corresponding auditory system. Spatial WM deficits may underlie some learning difficulties and behavioral problems related to impulsivity, difficulties in concentration, and hyperactivity. Alternatively, anxiety or depressive symptoms may affect WM function and the ability to concentrate, being thus the primary cause of poor academic achievement in children.

Expression of cytochrome P450 enzymes and metabolism of timolol in human ocular tissue

Glaucoma is a group of progressive optic neuropathies causing irreversible blindness if not diagnosed and treated in the early state of progression. Disease is often, but not always, associated with increased intraocular pressure (IOP), which is also the most important risk factor for glaucoma. Ophthlamic timolol preparations have been used for decades to lower increased intraocular pressure (IOP). Timolol is locally well tolerated but may cause e.g. cardiovascular and pulmonary adverse effects due to systemic absorption. It has been reported that approximately 80% of a topically administered eye drop is systemically absorbed. However, only limited information is available on timolol metabolism in the liver or especially in the human eye. The aim of this work was to investigate metabolism of timolol in human liver and human ocular tissues. The expression of drug metabolizing cytochrome P450 (CYP) enzymes in the human ciliary epithelial cells was studied. The metabolism of timolol and the interaction potential of timolol with other commercially available medicines were investigated in vitro using different liver preparations. The absorption of timolol to the aqueous humor from two commercially available products: 0.1% eye gel and 0.5% eye drops and the presence of timolol metabolites in the aqueous humor were investigated in a clinical trial. Timolol was confirmed to be metabolized mainly by CYP2D6 as previously suggested. Potent CYP2D6 inhibitors especially fluoxetine, paroxetine and quinidine inhibited the metabolism of timolol. The inhibition may be of clinical significance in patients using ophthalmic timolol products. CYP1A1 and CYP1B1 mRNAs were expressed in the human ciliary epithelial cells. CYP1B1 was also expressed at protein level and the expression was strongly induced by a known potent CYP1B1 inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The CYP1B1 induction is suggested to be mediated by aryl hydrocarbon receptor (AHR). Low levels of CYP2D6 mRNA splice variants were expressed in the human ciliary epithelial cells and very low levels of timolol metabolites were detected in the human aqueous humor. It seems that negligible amount of CYP2D6 protein is expressed in the human ocular tissues. Timolol 0.1% eye gel leads to aqueous humor concentration high enough to achieve therapeutic effect. Inter-individual variation in concentrations is low and intraocular as well as systemic safety can be increased when using this product with lower timolol concentration instead of timolol 0.5% eye drops.

The role of catechol-O-methyltransferase (COMT) and the effects of COMT inhibition in brain and in cardiovascular and renal pathophysiology

Catechol-O-methyltransferase (COMT) metabolizes catecholamines such as dopamine (DA), noradrenaline (NA) and adrenaline, which are vital neurotransmitters and hormones that play important roles in the regulation of physiological processes. COMT enzyme has a functional Val158Met polymorphism in humans, which affects the subjects COMT activity. Increasing evidence suggests that this functional polymorphism may play a role in the etiology of various diseases from schizophrenia to cancers. The aim of this project was to provide novel biochemical information on the physiological and especially pathophysiological roles of COMT enzyme as well as the effects of COMT inhibition in the brain and in the cardiovascular and renal system. To assess the roles of COMT and COMT inhibition in pathophysiology, we used four different study designs. The possible beneficial effects of COMT inhibition were studied in double-transgenic rats (dTGRs) harbouring human angiotensinogen and renin genes. Due to angiotensin II (Ang II) overexpression, these animals exhibit severe hypetension, cardiovascular and renal end-organ damage and mortality of approximately 25-40% at the age of 7-weeks. The dTGRs and their Sprague-Dawley controls tissue samples were assessed with light microscopy, immunohistochemistry, reverse transcriptase-polymerase chain reaction (RT-PCR) and high-pressure liquid chromatography (HPLC) to evaluate the tissue damages and the possible protective effects pharmacological intervention with COMT inhibitors. In a second study, the consequence of genetic and pharmacological COMT blockade in blood pressure regulation during normal and high-sodium was elucidated using COMT-deficient mice. The blood pressure and the heart rate were measured using direct radiotelemetric blood pressure surveillance. In a third study, the effects of acute and subchronic COMT inhibition during combined levodopa (L-DOPA) + dopa decarboxylase inhibitor treatment in homocysteine formation was evaluated. Finally, we assessed the COMT enzyme expression, activity and cellular localization in the CNS during inflammation-induced neurodegeneration using Western blotting, HPLC and various enzymatic assays. The effects of pharmacological COMT inhibition on neurodegeneration were also studied. The COMT inhibitor entacapone protected against the Ang II-induced perivascular inflammation, renal damage and cardiovascular mortality in dTGRs. COMT inhibitors reduced the albuminuria by 85% and prevented the cardiovascular mortality completely. Entacapone treatment was shown to ameliorate oxidative stress and inflammation. Furthermore, we established that the genetic and pharmacological COMT enzyme blockade protects against the blood pressure-elevating effects of high sodium intake in mice. These effects were mediated via enhanced renal dopaminergic tone and suggest an important role of COMT enzyme, especially in salt-sensitive hypertension. Entacapone also ameliorated the L-DOPA-induced hyperhomocysteinemia in rats. This is important, since decreased homocysteine levels may decrease the risk of cardiovascular diseases in Parkinson´s disease (PD) patients using L-DOPA. The Lipopolysaccharide (LPS)-induced inflammation and subsequent delayed dopaminergic neurodegeneration were accompanied by up-regulation of COMT expression and activity in microglial cells as well as in perivascular cells. Interestingly, similar perivascular up-regulation of COMT expression in inflamed renal tissue was previously noted in dTGRs. These results suggest that inflammation reactions may up-regulate COMT expression. Furthermore, this increased glial and perivascular COMT activity in the central nervous system (CNS) may decrease the bioavailability of L-DOPA and be related to the motor fluctuation noted during L-DOPA therapy in PD patients.